In Reply: Dr Martineau and Mr Jolliffe critique the exclusion of participants with prevalent disease from our study. We chose to maximize internal validity and focus specifically on investigating whether genetic variation modified the association of low 25-hydroxyvitamin D with the risk of incident disease outcomes in primarily older adults. It was an important first step to evaluate effect-modifying variants in a well-defined population with systematic, adjudicated ascertainment of incident events and for which there has been consistent evidence in the literature of vitamin D–disease relationships.